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Issue 23, Volume 128

Cover Figure:  Cleavage of Bcl-xL required for uptake of exosomes by myeloma/lymphoma cells.  See the article by Vardaki et al.

WASHINGTON, December 8, 2016 – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, PhD, and Deputy Editor Nancy Berliner, MD.

Hedgehog pathway activation in T-cell acute lymphoblastic leukemia predicts response to SMO and GLI1 inhibitors
Dagklis et al identify hyperactivation of the hedgehog developmental pathway in a subgroup of T-cell acute lymphoblastic leukemias. Given the availability of hedgehog-inhibiting drugs, this discovery may present a new therapeutic opportunity.

Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma
The investigators demonstrate a high frequency of NFKBIE deletions in primary mediastinal B-cell lymphoma (PMBL), report that these aberrations predict for poor outcomes, and further suggest that they play an important role in lymphomagenesis.

Inhibition of interleukin-1 signaling enhances elimination of tyrosine kinase inhibitor–treated CML stem cells
and
IL1RAP antibodies block IL-1–induced expansion of candidate CML stem cells and mediate cell killing in xenograft models
These 2 reports showthat increased expression of the IL-1 receptor complex confers a selective growth and survival advantage on chronic myeloid leukemia (CML) stem cells, and provide evidence that blocking IL-1 signaling has therapeutic potential at the stem cell level.

Reversible binding of hemoglobin to band 3 constitutes the molecular switch that mediates O2 regulation of erythrocyte properties
Chu et al show that oxygen changes the conformation of hemoglobin and modulates various red cell properties by altering its interaction with band 3, the major red cell membrane protein.

Inverse agonism at the P2Y12 receptor and ENT1 transporter blockade contribute to platelet inhibition by ticagrelor
Aungraheeta and colleagues describe a novel property of the antiplatelet drug ticagrelor in its interaction with the platelet adenosine diphosphate (ADP) P2Y12 receptor.

How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients
This How I Treat article addresses the background and practical approach to the treatment of resistant cytomegalovirus (CMV) infection in the stem cell transplant recipient. It highlights CMV virology, antiviral mechanisms, novel antiviral drugs, and clinical approaches to the treatment of CMV resistance in these high-risk patients.

MGUS to myeloma: a mysterious gammopathy of underexplored significance
In a Perspective, Dhodapkar offers a synthetic overview of the current knowledge of monoclonal gammopathy of undetermined significance (MGUS) biology and discusses future perspectives. He makes a special case for further exploring the role of the tumor microenvironment in MGUS progression and for moving therapy to earlier stages of disease.

Strategies before, during, and after hematopoietic cell transplantation to improve T-cell immune reconstitution
This review summarizes the current state of knowledge of T-cell immune reconstitution after stem cell transplantation and deals with stem cell source, pretransplant conditioning, microbiota/nutrition, and interventional strategies.

Haploidentical hematopoietic transplantation for the cure of leukemia: from its biology to clinical translation
This short review discusses current approaches to haploidentical transplantation for patients with leukemia, including the promising strategy of adoptive immunotherapy with thymus-derived/natural CD4+CD25+FoxP3+ regulatory T cells (Tregs) in combination with conventional T cells.

Human CalDAG-GEFI deficiency increases bleeding and delays αIIbβ activation
RASGRP2 encodes an abundant protein in platelets known as calcium- and diacylglycerol-regulated guanine nucleotide exchange factor I (CalDAG-GEFI). Kato et al identify compound heterozygous mutations in the RASGRP2 gene that cause decelerated platelet signaling, reduced platelet aggregation, and severe bleeding.

 

This week's complete table of contents

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Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.

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